Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approa
- PDF / 2,747,181 Bytes
- 25 Pages / 595.276 x 790.866 pts Page_size
- 76 Downloads / 225 Views
MEETING REPORTS
Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non‑genotoxic carcinogens Miriam N. Jacobs1 · Annamaria Colacci2 · Raffaella Corvi3 · Monica Vaccari2 · M. Cecilia Aguila4 · Marco Corvaro5 · Nathalie Delrue6 · Daniel Desaulniers7 · Norman Ertych8 · Abigail Jacobs4 · Mirjam Luijten9 · Federica Madia3 · Akiyoshi Nishikawa10 · Kumiko Ogawa10 · Kiyomi Ohmori11 · Martin Paparella12 · Anoop Kumar Sharma13 · Paule Vasseur14 Received: 14 April 2020 / Accepted: 7 May 2020 © The Author(s) 2020
Abstract While regulatory requirements for carcinogenicity testing of chemicals vary according to product sector and regulatory jurisdiction, the standard approach starts with a battery of genotoxicity tests (which include mutagenicity assays). If any of the in vivo genotoxicity tests are positive, a lifetime rodent cancer bioassay may be requested, but under most chemical regulations (except plant protection, biocides, pharmaceuticals), this is rare. The decision to conduct further testing based on genotoxicity test outcomes creates a regulatory gap for the identification of non-genotoxic carcinogens (NGTxC). With the objective of addressing this gap, in 2016, the Organization of Economic Cooperation and Development (OECD) established an expert group to develop an integrated approach to the testing and assessment (IATA) of NGTxC. Through that work, a definition of NGTxC in a regulatory context was agreed. Using the adverse outcome pathway (AOP) concept, various cancer models were developed, and overarching mechanisms and modes of action were identified. After further refining and structuring with respect to the common hallmarks of cancer and knowing that NGTxC act through a large variety of specific mechanisms, with cell proliferation commonly being a unifying element, it became evident that a panel of tests covering multiple biological traits will be needed to populate the IATA. Consequently, in addition to literature and database investigation, the OECD opened a call for relevant assays in 2018 to receive suggestions. Here, we report on the definition of NGTxC, on the development of the overarching NGTxC IATA, and on the development of ranking parameters to evaluate the assays. Ultimately the intent is to select the best scoring assays for integration in an NGTxC IATA to better identify carcinogens and reduce public health hazards. Keywords Non-genotoxic carcinogenicity · Integrated approaches to testing and assessment · IATA · Cancer hallmarks · Hazard assessment · Cancer prevention · Cancer model · Cancer microenvironment Abbreviations AR Androgen receptor AOP Adverse outcome pathway BMD Benchmark dose
Abigail Jacobs: FDA retired. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00204-020-02784-5) contains supplementary material, which is available to authorized users. * Miriam N. Jacobs [email protected] Extended author infor
Data Loading...
